2023 World Conference on Lung Cancer (Posters)-P2.10. Co-occurring Loss of CDKN2A/2B Associated with Worse Survival and Increase Risk of Brain Metastasis in ALK-Rearranged Non-small Cell Lung Cancer

P2.10. Co-occurring Loss of CDKN2A/2B Associated with Worse Survival and Increase Risk of Brain Metastasis in ALK-Rearranged Non-small Cell Lung Cancer - PDF(Abstract)

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A study presented at the WCLC 2023 conference analyzed the impact of co-occurring genetic alterations on the survival outcomes of patients with metastatic ALK-rearranged non-small cell lung cancer (NSCLC) who received second-generation ALK tyrosine kinase inhibitors (TKIs). The study cohort included 125 tumor specimens from Latin-American cancer centers. The most common fusion partner was EML4-ALK, and the most common variant was 3a/b. Co-occurring alterations occurred in 62% of cases, with TP53 mutations and loss of CDKN2A/B being the most frequent. Loss of CDKN2A/B was significantly associated with an increased risk of brain metastasis at diagnosis. The cumulative incidence of brain metastasis was much higher in tumors with a concurrent loss of CDKN2A/B compared to those without. The majority of patients received alectinib as the preferred ALK-TKI. The median progression-free survival (PFS) and overall survival (OS) in the total patient population were 30.3 months and 80.6 months, respectively. Patients with a concurrent loss of CDKN2A/B had significantly shorter median PFS and OS compared to those without this co-alteration. In the multivariate analysis, a loss of CDKN2A/B remained associated with poorer PFS and OS, independent of other co-alterations, TP53 mutations, brain metastasis, and ECOG PS. The study highlights the prognostic value of co-occurring alterations in ALK-rearranged NSCLC and specifically identifies the loss of CDKN2A/B as significantly impacting outcomes and increasing the risk of brain metastasis. This information can help in determining suitable therapeutic strategies and the need for closer brain monitoring for patients with ALK-positive tumors.

Asset Subtitle

Oscar ARRIETA

Meta Tag

Speaker Oscar ARRIETA

Topic Metastatic NSCLC: Targeted Therapy - FUSIONS

Keywords

genetic alterations

survival outcomes

metastatic ALK-rearranged NSCLC

ALK tyrosine kinase inhibitors

Latin-American cancer centers

TP53 mutations

loss of CDKN2A/B

brain metastasis

alectinib

prognostic value